HO-1 expression in type II pneumocytes after transpulmonary gene delivery

Somatic cell gene transfer is a potentially useful strategy to alter lung f unction. However, achieving efficient transfer to the alveolar epithelium, especially in smaller animals, has not been demonstrated. In this study, th e rat heme oxygenase-1 (HO-1) gene was delivered to the lungs of neonatal m ice via transpulmonary injection. A bidirectional promoter construct coexpr essing both HO-1 and a luciferase reporter gene was used so that in vivo ge ne expression patterns could be monitored in real time. HO-1 expression lev els were also modulated with doxycycline and assessed in vivo with biolumin escent light transmitted through the tissues from the coregulated luciferas e reporter. As a model of oxidative stress and HO-1-mediated protection, gr oups of animals were exposed to hyperoxia. After gene transfer, elevated le vels of HO-1 were detected predominantly in alveolar type II cells by immun ocytochemistry. With overexpression of HO-1, increased oxidative injury was observed. Furthermore, this model demonstrated a cell-specific effect of l ung HO-1 overexpression in oxidative stress. Specific control of expression for therapeutic genes is possible in vivo. The transpulmonary approach may prove useful in targeting gene expression to cells of the alveolar epithel ium or to circumscribed areas of the lung.